Biguanide derivatives, manufacturing method thereof, and disinfectants containing the derivatives

ABSTRACT

The invention presents a biguanide derivative or its salt expressed by a formula: ##STR1## (where R 1  and R 2  are as defined in Specification), or formula: ##STR2## (where A and R 3  is as defined in specification). This biguanide derivative or its salt is preferably used as the effective amount of a disinfectant for humans, animals, medical appliances, etc.

BACKGROUND OF THE INVENTION

The invention relates to novel biguanide derivatives used indisinfection of humans, animals, medical appliances, and others, amethod of manufacturing the same, and disinfectants containing suchderivatives.

It is known that various guanidine derivatives possess bactericidalactions, and biguanide derivatives of 1,4-dimethylene cyclohexane typeare disclosed in the British Patent Specification No. 1,098,902.

SUMMARY OF THE INVENTION

It is a primary object of this invention to present novel biguanidederivatives or their salts possessing a higher activity than theconventional biguanide derivatives or their salts, and disinfectantscontaining such derivatives or their salts.

To achieve the above object, a monobiguanide derivative of the inventionis a biguanide derivative or its salt, expressed by a general formula:##STR3## (where R¹ represents 3,4-dichlorobenzyl group, 4-chlorophenylgroup, 3,4-dichlorophenyl group, benzyl group or 4-chlorobenzyl group,and R² represents octyl group, 3,4-dichlorobenzyl group, dodecyl group,decyl group, 3-trifluoromethylphenyl group, 4-bromophenyl group,4-iodophenyl group, 2,4-dichlorophenyl group, 3,4-dichlorophenyl group,2,3,4-trichlorophenyl group, 3,4-dimethylphenyl group,3,4-methylenedioxyphenyl group, 4-t-butylphenyl group, 4-ethylthiophenylgroup, 1,1,3,3-tetramethylbutyl group, hexyl group, 2-ethoxyethyl group,2-(2-hydroxyethoxy)ethyl group, 3-diethylaminopropyl group,3-(2-ethylhexyloxy)-propyl group, (3-isopropoxy)propyl group,(2-diethylamino)-ethyl group, (3-butyl)-propyl group,3(di-n-butylamino)propyl group, cyclohexylmethyl group,3-trifluoromethylphenyl group, 4-ethylthiophenyl group, 4-chlorobenzylgroup, 2,4-dichlorobenzyl group, 4-acetylaminophenyl group,3,4-methylenedioxyphenyl group, 3,4-methylenedioxybenzyl group, octylgroup, 4-chlorobenzyl group, decyl group, dodecyl group, isobutyl group,3,4-dichlorophenyl group, or hexyl group), and the derivative being N¹-(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(3,4-dichlorobenzyl)-biguanide,

N¹ -(3,4-dichlorophenyl)-N⁵ -octyl-biguanide,

N¹ -benzyl-N⁵ -dodecyl-biguanide,

N¹ -benzyl-N⁵ -decyl-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(3-trifluoromethylphenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(4-bromophenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(4-iodophenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(2,4-dichlorophenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(3,4-dichlorophenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(2,3,4-trichlorophenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(3,4-dimethylphenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(3,4-methylenedioxyphenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(4-t-butylphenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(4-ethylthiophenyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(n-decyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(1,1,3,3-tetramethylbutyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -hexyl-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(2-ethoxyethyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -[2-(2-hydroxyethoxy) ethyl]-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -(3-diethylaminopropyl)-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -[3-(2-ethylhexyloxy)propyl]-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -[(3-isopropoxy)propyl]-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -[(2-diethylamino)-ethyl]-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -[(3-butyl)-propyl]-biguanide,

N¹ -(3,4-dichlorobenzyl)-N⁵ -[3(di-n-butylamino)propyl]-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -cyclohexylmethyl-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(3-trifluoromethylphenyl)-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(4-ethylthiophenyl)-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(4-chlorobenzyl)-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(2,4-dichlorobenzyl)-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(4-acetylaminophenyl)-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(3,4-methylenedioxyphenyl)-biguanide,

N¹ -(4-chlorophenyl)-N⁵ -(3,4-methyleneoxydibenzyl)-biguanide,

N¹ -(4-chlorobenzyl)-N⁵ -octyl-biguanide,

N¹ -(4-chlorobenzyl)-N⁵ -(4-chlorobenzyl)-biguanide,

N¹ -(4-chlorobenzyl)-N⁵ -decyl-biguanide,

N¹ -(4-chlorobenzyl)-N⁵ -dodecyl-biguanide,

N¹ -(4-chlorobenzyl)-N⁵ -isobutyl-biguanide,

N¹ -(4-chlorobenzyl)-N⁵ -(3,4-dichlorophenyl)-biguanide,

N¹ -(3,4-dichlorophenyl)-N⁵ -(3,4-methylenedioxybenzyl)-biguanide,

N¹ -(3,4-dichlorophenyl)-N⁵ -hexyl-biguanide,

N¹ -(3,4-dichlorophenyl)-N⁵ -decyl-biguanide.

The biguanide derivative (1) or its salt of the invention possesses ahigher bactericidal action or anti-bacterial action than a knownbiguanide. Therefore, the disinfectant of the invention contains thebiguanide derivative expressed by Formula (1) or its salt as an activeingredient.

This invention also presents a novel bis-biguanide derivative or itssalt expressed by a general formula (2): ##STR4## (where R³ representsphenyl group which may posess one to three groups selected from a groupconsisting of halogen atom, lower alkyl group, halogen substituted loweralkyl group and lower alkylthio group as substituent; phenyl lower alkylgroup which may possess a halogen atom as substituent on phenyl ring; oralkyl group, and A denotes a lower alkylene group).

The biguanide derivative (2) or its salt also possesses a highbactericidal action or antibacterial action same as the biguanidederivative (1). Therefore, the other disinifectant of this inventioncontains the bis-biguanide derivative expressed by Formula (2) or itssalt as an active ingredient.

In the following explanation, the compound expressed by the generalformula (1) is called as a monobiguanide derivative, and the compoundexpressed in Formula (2) is called a bis-biguanide derivative.

DETAILED DESCRIPTION OF THE INVENTION

The monobiguanide derivative expressed by Formula (1) or its salt of theinvention is specifically represented in the Examples hereinafter.

The monobiguanide derivative (1) of the invention is a basic compound,and forms a corresponding acid-addition salt by reacting with an organicacid or an inorganic acid. Acids for forming such salt may include, forexample, formic acid, acetic acid, lactic acid, butyric acid, isobutyricacid, α-mercaptopropionic acid, trifluoroacetic acid, malic acid,fumaric acid, succinic acid, succinic monoamide, glutamic acid, tartaricacid, oxalic acid, citric acid, glycolic acid, gluconic acid, saccharicacid, ascorbic acid, penicillin, benzoic acid, phthalic acid, salicylicacid, anthranilic acid, benzenesulfonic acid, p-toluenesulfonic acid,methansulfonic acid, hydrochloric acid, hydrobromic acid, sulfuric acid,phosphoric acid, nitric acid and carbonic acid, and are not particularlylimited. Besides, the ratio of monobiguanide derivative and acid forforming acid-addition salt is not particularly limited, and salts ofvarious ratios may be used such as 1:1, 1:2, or the like.

The acid-addition salt is manufactured in an ordinary salt formingmethod, such as direct mixing of acid and base, dissolving one or bothin solvent such as water and mixing, and charging acid or base insolvent to dissolve and mix. After reaction, the obtained acid-additionsalt is filtered if insoluble or hardly soluble in reaction medium, orrecovered by evaporating the reaction medium if soluble in the reactionmedium.

Such acid-addition salt itself exhibits a high bactericidal effect orantibacterial effect, and is also useful for refining or isolation offree base. Meanwhile, the acid-addition salt is preferred to beacceptable pharmaceutically.

The monobiguanide derivative (1) of this invention may also form astable coordination compound with a metal salt. Such coordinationcompound also presents a bactericidal effect. The coordination compoundis obtained by reaction of its derivative or its acid-adition salt witha specified quantity of metal salt, preferably a heavy metal salt suchas V, Cr, Mn, Co, Ni, Cu, Zn, Pd, Re and Os.

Next is explained a manufacturing method of the monobiguanide derivative(1) of the invention. ##STR5## (where R¹ and R² are same as definedabove.)

As shown in the reaction formula above, the monobiguanide derivative (1)of the invention is obtained by reaction of the amine expressed byFormula (a) with N¹ -cyanoguanidine compound expressed by Formula (b).At this time, the amine (a) is used in about equimolecular amounts ofthe compound (b). The amine (a) may be used in a form of properacid-addition salt such as hydrochloric acid salt.

The both components (a) and (b) are caused to react by heating in thepresence or absence of inert solvent, such as 2-ethoxyethanol,2-methoxyethanol and o-dichlorobenzene. If the product is anacid-addition salt, it may be changed into a form of free base bycausing an alkali such as sodium hydroxide to act thereon, or may bechanged into other acid-addition salt by ion exchange or other process.

The starting material expressed by Formula (b) may be manufactured, forexample, in the following reaction formula. ##STR6## (where M representsan alkali metal, and R² is same as defined above.)

That is, the amine expressed by Formula (c) or its acid-addition salt(hydrochloride, etc.) is caused to react with the alkali metal salt (d)of dicyanamide (for example, sodium dicyanamide, potassium dicyanamide)in an inert solvent to obtain the material.

The monobiguanide derivative (1) of this invention may be alsomanufactured in the following reaction formula. ##STR7## (where R¹ andR² represent the same as above.)

This reaction is performed nearly in the same condition as in the abovereaction.

The bis-biguanide derivative (2) of this invention is described below.Examples of halogen atom represented by R³ in Formula (3) may includechlorine, bromine, iodine and fluorine.

Examples of lower alkyl group include straight-chain or branched alkylgroup having 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, tert-butyl, n-amyl, n-hexyl group, and thelike.

Examples of halogen substituted lower alkyl group include halogensubstitued lower alkyl group having 1 to 6 carbon atoms and replaced by1 to 3 halogen atoms, such as monochloromethyl, monobromomethyl,monofluoromethyl, monoiodomethyl, dichloromethyl, dibromomethyl,difluoromethyl, diiodomethyl, trichloromethyl, tribromomethyl,trifluoromethyl, triiodomethyl, 3-chloropropyl, 3-fluoropropyl,2,3-dichloropropyl, 3,3,3-trichloropropyl, 3-chloro-2-methylpropyl,4-chlorobutyl, 4-fluorobutyl, 5-chloropentyl, 6-chlorohexyl,6-fluorohexyl group, and the like.

Examples of lower alkylthio group include lower alkylthio group havingstraight-chain or branched alkyl moiety having 1 to 6 carbon atoms, suchas methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio,isobutylthio, tert-butylthio, n-amylthio, n-hexylthio group, and thelike.

Examples of phenyl lower alkyl group which may possess a halogen atom ona phenyl group as a substituent may include phenyl lower alkyl grouppossessing one to three phenyl groups which may have one to threehalogen atoms, and having 1 to 6 carbon atoms in the alkyl moiety, suchas benzyl, α-phenethyl, β-phenethyl, 3-phenylpropyl group, benzhydryl,trithyl, 4-chlorophenylmethyl, 3-chlorophenylmethyl,2-chlorophenylmethyl, 3,4-dichlorophenylmethyl, 4-fluorophenylmethyl,3,4-difluorophenylmethyl, 4-chlorophenylethyl, 3,4-dichlorophenylethylgroup, and the like.

Examples of alkyl group used as subsituent R³ are straight-chain orbranched alkyl groups having 6 to 16 carbon atoms, specificallyincluding n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl,n-tetradecyl, n-hexadecyl, 2-ethyl-1-hexyl, 2-ethyl-1-heptyl, 2-heptyl,2-octyl, and 1,1,3,3-tetramethylbutyl group.

Examples of lower alkylene group include alkylene group having 1 to 6carbon atoms, such as methylene, methylmethylene, ethylene,dimethylmethylene, trimethylene, 1-methyl-1-trimethyl,2-methyltrimethylene, 2,2-dimethyltrimethylene, tetramethylene,pentamethylene, hexamethylene, and the like.

Practical examples of the bis-biguanide derivative (2) of the inventionare shown in the table below. ##STR8##

    ______________________________________                                        R.sup.3            A                                                          ______________________________________                                                           CH.sub.2                                                    ##STR9##          "                                                           ##STR10##         "                                                           ##STR11##         "                                                           ##STR12##         "                                                           ##STR13##         "                                                           ##STR14##         "                                                           ##STR15##         "                                                           ##STR16##         "                                                           ##STR17##         "                                                           ##STR18##         CH.sub.2                                                    ##STR19##         "                                                           ##STR20##         "                                                           ##STR21##         CH.sub.2 CH.sub.2                                           ##STR22##         "                                                           ##STR23##         CH.sub.2                                                    ##STR24##         "                                                           ##STR25##         "                                                           ##STR26##         (CH.sub.2 ) .sub.3                                         H.sub.3 C          CH.sub.2                                                   (H.sub.3 C).sub.3 C                                                                              "                                                          ______________________________________                                    

The bis-biguanide derivative (2) of this invention is a basic compound,and forms, same as the monobiguanide derivative (1), a correspondingacid-addition salt by reaction with various organic acids or inorganicacids.

The acid-addition salt of the bis-biguanide derivative (2) itself, aswell as its derivative (2), exhibits a high bactericidal effect orantibacterial effect, and it is also useful for refining or isolation offree base. The acid-addition salt is preferred to be acceptablepharmaceutically. The bis-biguanide derivative (2) of the invention,same as the monobiguanide derivative (1), may also form a stablecoordination compound with a metal salt, and such coordination compoundalso presents an excellent bactericidal effect.

The bis-biguanide derivative (2) of the invention is manufactured, forexample, in the following reaction formula. ##STR27## (where A and R³represent same as defined above.)

As shown in the reaction formula above, the bis-biguanide derivative (2)of this invention is obtained by the reaction of1,1'-[1,3-cyclohexanebis(alkylene)]-bis(3-cyanoguanidine) shown inFormula (e) with the amine shown in Formula (f). At this time, the amine(f) is used by about twice the tool equivalent of the compound (e). Theamine (f) may be in a form of proper acid-addition salt such ashydrochloride.

The both components (e) and (f) are caused to react with each other byheating in the presence or absence of an inert solvent (e.g.2-ethoxyethanol, 2-methoxyethanol, o-dichlorobenzene). If the reactionproduct is an acid-addition salt, it may be changed into a form of afree base by causing an alkali such as sodium hydroxide to act thereon,or changed into other acid-addition salt by ion exchange or otherprocess.

The starting material expressed by Formula (e) may be manufactured, forexample, in the following reaction formula. ##STR28## (where M denotesan alkali metal, and A is same as defined above.)

It is obtained, accordingly, by reaction of the diamine shown in Formula(g) or its acid-addition salt (hydrochloride, etc.) with the alkalimetal salt (h) of dicyanamide (e.g. sodium dicyanamide, potassiumdicyanamide) in an inert solvent.

The bis-biguanide derivative (2) of this invention may be alsomanufactured in the following reaction formula. ##STR29## (where A andR³ represent the same as above.)

As shown in the above reaction formula, the bis-biguanide derivative (2)is obtained by the reaction between the diamine expressed by Formula (i)or its acid-addition salt (hydrochloride, etc.) and the cyanoguanidinecompound expressed by Formula (j), in the presence or absence of aninert solvent. The reaction is conducted under heating. Thecyanoguanidine compound (j) is used at a rate of about twice the molequivalent of the diamine (i).

The biguanide derivatives (1), (2) of this invention and their saltspossess higher antibacterial activities (bactericidal action orantibacterial action) as compared with the hitherto known biguanidederivatives, and some of them also possess antiviral activity.Furthermore, the biguanide derivatives (1), (2) of the invention andtheir salts possess a broad antibacterial spectrum, and are alsoexcellent in rapidity of action, stability, safety and others, and theiractivities last for a long time. In addition, they are stimulation-free,odor-free, and soluble also in water. In particular, the compounds inExamples 1 to 4 mentioned below and their salts are particularlyexcellent in these features, and above all the compound of Example 1 andits salt are excellent in, including the above features, broadantibacterial spectrum, high short-time bactericidal activity,long-lasting drug effect, no problem in color, odor and taste, lowtoxicity, and the like. The salt of the compound of this invention isexcellent in various points, including the above features, such as highsolubility, low stimulation and toxicity, high stability, and the like.

Therefore, the biguanide derivatives (1), (2) of this invention andtheir salts are useful as active ingredient for disinfectants forhumans, animals, and medical appliances. The disinfectant of thisinvention is used in a form of solution, dispersion or suspension bydissolving, dispersing or suspending a specified amount of the biguanidederivatives (1), (2) or their salts in water or organic solvent. Typicalexamples are eye-drop, nose-drop, gargle, detergent, cleaning agent, andother external application liquids. In these cases, the content of thebiguanide derivatives (1), (2) or their salts may be usually about 0.01to 20% by weight of the total amount.

Besides, the biguanide derivatives (1), (2) of this invention and theirsalts may be contained in various cosmetics, such as creams, lotions,powders, colors, makeups, toothpaste, shampoo, soap, depilatories,bleaches, hair-dyes, hair tonics, bath additives, manicure,antiperspiration agent, deodorant, aerosol cosmetics, and babycosmetics, and the like.

Cosmetics are manufactured by dissolving, dispersing or suspending thespecified amount of the biguanide derivatives (1), (2) or their salts,together with other ingredients, in water, other solvent, or variouscosmetic bases. The content of the biguanide derivative (1), (2) ortheir salts in the cosmetic is usually about 0.001 to 1% by weight ofthe total amount.

EXAMPLES

Referring to examples, the biguanide derivative of this invention andthe disinifectant containing the derivative are explained in detailbelow. It must be, however, noted that this invention is not limited tothese examples.

EXAMPLE 1 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidehydrochloride

To 20 g of N¹ -cyano-N³ -octyl-guanidine and 20.2 g of3,4-dichlorobenzylamine hydrochloride, 200 ml of mesitylene was added,which was heated and refluxed for 1.5 hours. Returning to roomtemperature after reaction, mesitylene was removed. To the residue, 200ml of 10% ethanol aqueous solution was added, which was heated, andstirred for 3 hours at room temperature to be solidified. It wasfiltered off, and washed with 10% ethanol solution, water andisopropylether in turn, and 28.1 g of rough product was obtained. It wasrecrystallized in ethyl acetate, and 22.1 g of the captioned compoundwas obtained.

White edged crystals mp. 177°˜179° C.

Elemental analysis C₁₇ H₂₈ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   49.95         6.90   17.13                                           Found    49.67         7.18   17.01                                           ______________________________________                                    

EXAMPLE 2 Preparation of N¹ -(4-chlorophenyl)-N⁵-(3,4-dichlorobenzyl)-biguanide hydrochloride

To 20 g of N¹ -cyano-N³ -(3,4-dichlorobenzyl)-guanidine and 13.5 g of4-chloroaniline hydrochloride, 200 ml of water was added, which washeated and refluxed for 2 hours. When cooled gradually after reaction,crystals was precipiated. After filtering the crystals, by drying thecrystals obtained by heat treatment in 200 ml of ethyl acetate, 21.8 gof the captioned compound was obtained.

White edged crystals mp. 238°˜240° C.

Elemental analysis C₁₅ H₁₅ Cl₄ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   44.25         3.71   17.20                                           Found    44.19         3.66   17.17                                           ______________________________________                                    

EXAMPLE 3 Preparation of N¹ -(3,4-dichlorophenyl)-N⁵ -octyl-biguanidehydrochloride

In the same procedure as in Example 1 except that3,4-dichlorobenzylamine hydrochloride was replaced by the equimolecularamount of 3,4-dichloroaniline hydrochloride, 28.2 g of the captionedcompound was obtained.

White edged crystals mp. 176°˜177° C.

Elemental analysis C₁₆ H₂₆ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   48.68         6.64   17.74                                           Found    48.52         6.50   17.77                                           ______________________________________                                    

EXAMPLE 4 Preparation of N¹ -benzyl-N⁵ -dodecyl-biguanide hydrochloride

To 20 g of N¹ -cyano-N³ -benzyl-guanidine and 25.4 g of dodecylaminehydrochloride, 200 ml of mesitylene was added, which was heated andrefluxed for 2 hours. After reaction, by the same operation as inExample 1, 23.7 g of the captioned compound was obtained.

White edged crystals mp. 135°˜137° C.

Elemental analysis C₂₁ H₃₈ ClN₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   63.69         9.67   17.68                                           Found    63.47         9.41   17.73                                           ______________________________________                                    

EXAMPLE 5 Preparation of N¹ -benzyl-N⁵ -decyl-biguanide hydrochloride

In the same manner as in Example 4 except that dodecylaminehydrochloride was replaced by the equimolecular amount of decylaminehydrochloride, 20.3 g of the captioned compound was obtained.

White edged crystals mp. 133°˜135° C.

Elemental analysis C₁₉ H₃₄ ClN₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   62.02         9.31   19.03                                           Found    62.29         9.57   18.91                                           ______________________________________                                    

EXAMPLE 6 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(3-trifluoromethylphenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of3-trifluoromethylaniline hydrochloride, 23.2 g of the captioned compoundwas obtained.

White edged crystals mp. 185°˜188° C.

Elemental analysis C₁₆ H₁₅ Cl₃ F₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   43.61         3.43   15.89                                           Found    43.57         3.24   16.10                                           ______________________________________                                    

EXAMPLE 7 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(4-bromophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of 4-bromoanilinehydrochloride, 21.6 g of the captioned compound was obtained.

White edged crystals mp. 223°˜225° C.

Elemental analysis C₁₅ H₁₅ BrCl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   39.90         3.35   15.51                                           Found    40.34         3.16   15.82                                           ______________________________________                                    

EXAMPLE 8 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(4-iodophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of 4-iodoanilinehydrochloride, 22.6 g of the captioned compound was obtained.

White edged crystals mp. 215°˜217° C.

Elemental analysis C₁₅ H₁₅ Cl₃ IN₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   36.14         3.03   14.05                                           Found    36.25         2.80   14.21                                           ______________________________________                                    

EXAMPLE 9 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(2,4-dichlorophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of2,4-dichloroaniline hydrochloride, 20.4 g of the captioned compound wasobtained.

White edged crystals mp. 217°˜220° C.

Elemental analysis C₁₅ H₁₅ Cl₅ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   40.80         3.20   15.86                                           Found    41.25         2.93   15.79                                           ______________________________________                                    

EXAMPLE 10 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(3,4-dichlorophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of3,4-dichloroaniline hydrochloride, 21.7 g of the captioned compound wasobtained.

White edged crystals mp. 205°˜208° C.

Elemental analysis C₁₅ H₁₄ Cl₅ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   40.80         3.20   15.86                                           Found    41.03         2.94   15.94                                           ______________________________________                                    

EXAMPLE 11 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(2,3,4-trichlorophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of2,3,4-trichloroaniline hydrochloride, 23.2 g of the captioned compoundwas obtained.

White edged crystals mp. 227°˜228° C.

Elemental analysis C₁₅ H₁₃ Cl₆ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   37.85         2.75   14.71                                           Found    38.09         2.55   14.81                                           ______________________________________                                    

EXAMPLE 12 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(3,4-dimethylphenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of3,4-dimethylaniline hydrochloride, 20.3 g of the captioned compound wasobtained.

White edged crystals mp. 190°˜191° C.

Elemental analysis C₁₇ H₂₀ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   50.95         5.03   17.48                                           Found    50.66         4.78   17.56                                           ______________________________________                                    

EXAMPLE 13 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(3,4-methylenedioxyphenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of3,4-methylenedioxyaniline hydrochloride, 25.7 g of the captionedcompound was obtained.

White edged crystals mp. 204°˜206° C.

Elemental analysis C₁₆ H₁₆ Cl₃ N₅ O₂

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   46.12         3.87   16.81                                           Found    45.83         3.69   16.97                                           ______________________________________                                    

EXAMPLE 14 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(4-t-butylphenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of4-t-butylaniline hydrochloride, 22.5 g of the captioned compound wasobtained.

White edged crystals mp. 228°˜230° C.

Elemental analysis C₁₉ H₂₄ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   53.22         5.64   16.33                                           Found    52.93         5.38   16.16                                           ______________________________________                                    

EXAMPLE 15 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(4-ethylthiophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that 4-chloroanilinehydrochloride was replaced by the equimolecular amount of4-ethylthioaniline hydrochloride, 20.7 g of the captioned compound wasobtained.

White edged crystals mp. 199°˜200° C.

Elemental analysis C₁₇ H₂₀ Cl₃ N₅ S

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   47.18         4.66   16.18                                           Found    47.12         4.46   16.04                                           ______________________________________                                    

EXAMPLE 16 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(n-decyl)-biguanide hydrochloride

In the same manner as in Example 1 except that N¹ -cyano-N³-octyl-guanidine was replaced by the equimolecular amount of N¹-cyano-N³ -(n-decyl)-guanidine, 24.5 g of the captioned compound wasobtained.

White edged crystals mp. 135°˜137° C.

Elemental analysis C₁₉ H₃₂ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   52.24         7.38   16.03                                           Found    52.08         7.12   16.31                                           ______________________________________                                    

EXAMPLE 17 Preparation of N¹⁻ -(3,4-dichlorobenzyl)-N⁵-(1,1,3,3-tetramethylbutyl)-biguanide hydrochloride

In the same manner as in Example 1 except that N¹ -cyano-N ³-oxtyl-guanidine was replaced by the equimolecular amount of N¹-cyano-N³ -(1,1,3,3-tetrabutyl)-guanidine, 23.1 g of the captionedcompound was obtained.

White edged crystals mp. 196°˜198° C.

Elemental analysis C₁₇ H₂₈ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   49.95         6.90   17.13                                           Found    49.78         6.81   17.01                                           ______________________________________                                    

EXAMPLE 18 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -hexyl-biguanidehydrochloride

In the same manner as in Example 1 except that N¹ -cyano-N³-octyl-guanidine was replaced by the equimolecular amount of N¹-cyano-N³ -hexyl guanidine, 19.7 g of the captioned compound wasobtained.

White edged crystals mp. 155°˜157° C.

Elemental analysis C₁₅ H₂₄ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   47.32         6.35   18.39                                           Found    47.21         6.17   18.50                                           ______________________________________                                    

EXAMPLE 19 N¹ -(3,4-dichlorobenzyl)-N⁵ -(2-ethoxyethyl)-biguanidehydrochloride

In the same manner as in Example 1 except that N¹ -cyano-N³-octyl-guanidine was replaced by the equimolecular amount of N¹-cyano-N³ -(2-ethoxyethyl)-guanidine, 23.1 g of the captioned compoundwas obtained.

White edged crystals mp. 170°˜173° C.

Elemental analysis C₁₃ H₂₀ Cl₃ N₅ O

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   42.35         5.47   18.99                                           Found    42.09         5.18   18.73                                           ______________________________________                                    

EXAMPLE 20 N¹ -(3,4-dichlorobenzyl-N⁵-[2-(2-hydroxyethoxy)ethyl]-biguanide hydrochloride

In the same manner as in Example 1 except that N¹ -cyano-N³-octyl-guanidine was replaced by the equimolecular amount of N¹-cyano-N³ -[2-(2-hydroxyethoxy)ethyl]-guanidine, 21.5 g of the captionedcompound was obtained.

White edged crystals mp. 140°˜142° C.

Elemental analysis C₁₃ H₂₀ Cl₃ N₅ O₂

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   40.59         5.24   18.20                                           Found    40.30         5.01   18.03                                           ______________________________________                                    

EXAMPLE 21 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-(3-diethylaminopropyl)-biguanide

A rough product was obtained in the same manner as in Example 1 exceptthat N¹ -cyano-N³ -octyl-guanidine was replaced by the equimolecularamount of N¹ -cyano-N³ -(3-diethylaminopropyl)-guanidine. The productwas dissolved in 100 ml of methanol, and an equimolecular amount of 1Nsodium hydroxide was added, which was concentrated at reduced pressure,and the residue was recrystallized in isopropanol, and 16.7 of thecaptioned compound was obtained.

White edged crystals mp. 156°˜158° C.

Elemental analysis C₁₆ H₂₆ Cl₂ N₆

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   51.48         7.02   22.51                                           Found    51.21         6.83   22.76                                           ______________________________________                                    

In the following Examples 22 to 26, using proper starting materials, theindividual compounds were prepared in the same manner as in Example 1.

EXAMPLE 22 Preparation of N¹ -(3,4-Dichlorobenzyl)-N⁵-[3-(2-ethylhexyloxy)-propyl]-biguanide hydrochloride

White edged crystals mp. 200°˜203° C.

Elemental analysis C₂₀ H₃₄ Cl₃ N₅ O

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   51.45         7.34   15.00                                           Found    51.12         7.62   14.82                                           ______________________________________                                    

EXAMPLE 23 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-[(3-isopropoxy)propyl]-biguanide hydrochloride

White edged crystals mp. 158°˜160° C.

Elemental analysis C₁₅ H₂₄ Cl₃ N₅ O

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   45.41         6.10   17.65                                           Found    45.17         6.02   17.53                                           ______________________________________                                    

EXAMPLE 24 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-[(2-diethylamino)-ethyl]-biguanide

White edged crystals mp. 137°˜140° C.

Elemental analysis C₁₅ H₂₄ Cl₂ N₆

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   50.14         6.73   23.39                                           Found    50.01         6.48   23.15                                           ______________________________________                                    

EXAMPLE 25 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-[(3-butoxy)-propyl]-biguanide hydrochloride

White edged crystals mp. 181°˜184° C.

Elemental analysis C₁₆ H₂₆ Cl₃ N₅ O

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   46.78         6.38   17.05                                           Found    46.49         6.27   17.21                                           ______________________________________                                    

EXAMPLE 26 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵-[3-(di-n-butylamino)propyl] -biguanide dihydrochloride

White edged crystals mp, 122°˜124° C.

Elemental analysis C₂₀ H₃₆ Cl₄ N₆

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   47.82         7.22   16.73                                           Found    47.72         7.01   16.65                                           ______________________________________                                    

EXAMPLE 27 Preparation of N¹ -(4-chlorophenyl)-N⁵-cyclohexylmethyl-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³-(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amountof N¹ -cyano-N³ -cyclohexylmethyl-guanidine, 20.4 g of the captionedcompound was obtained.

White edged crystals mp. 240°˜241° C.

Elemental analysis C₁₅ H₂₃ Cl₂ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   52.33         6.73   20.34                                           Found    52.24         6.61   20.48                                           ______________________________________                                    

EXAMPLE 28 Preparation of N¹ -(4-chlorophenyl)-N⁵-(3-trifluoromethylphenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³-(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amountof N¹ -cyano-N³ -(3-trifluoromethylphenyl)-guanidine, 22.7 g of thecaptioned compound was obtained.

White edged crystals mp. 213°˜215° C.

Elemental analysis C₁₅ H₁₄ Cl₂ F₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   45.93         3.60   17.86                                           Found    46.03         3.55   18.04                                           ______________________________________                                    

EXAMPLE 29 Preparation of N¹ -(4-chlorophenyl)-N⁵-(4-ethylthiophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³-(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amountof N¹ -cyano-N³ -(4-ethylthiophenyl)-guanidine, 20.76 g of the captionedcompound was obtained.

White edged crystals mp. 243°˜245° C.

Elemental analysis C₁₆ H₁₉ Cl₂ N₅ S

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   50.00         4.98   18.22                                           Found    50.04         4.82   18.10                                           ______________________________________                                    

EXAMPLE 30 Preparation of N¹ -(4-chlorophenyl)-N⁵-(4-chlorobenzyl)-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³-(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amountof N¹ -cyano-N³ -(4-chlorobenzyl)-guanidine, 21.6 g of the captionedcompound was obtained.

White edged crystals mp. 225°˜227° C.

Elemental analysis C₁₅ H₁₆ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   48.34         4.33   18.79                                           Found    48.32         4.19   18.86                                           ______________________________________                                    

EXAMPLE 31 Preparation of N¹ -(4-chlorophenyl)-N⁵-(2,4-dichlorobenzyl)-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³-(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amountof N¹ -cyano-N³ -(2,4-dichlorobenzyl)-guanidine, 20.1 g of the captionedcompound was obtained.

White edged crystals mp. 234°˜236° C.

Elemental analysis C₁₅ H₁₅ Cl₄ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   44.25         3.71   17.20                                           Found    44.42         3.50   16.95                                           ______________________________________                                    

EXAMPLE 32 Preparation of N¹ -(4-chlorophenyl)-N⁵-(4-acetylaminophenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³-(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amountof N¹ -cyano-N³ -(4-acetylaminophenyl)-guanidine, 18.6 g of thecaptioned compound was obtained.

White edged crystals mp. 253°˜255° C.

Elemental analysis C₁₆ H₁₈ Cl₂ N₆ O

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   50.40         4.76   22.04                                           Found    50.63         4.51   21.92                                           ______________________________________                                    

EXAMPLE 33 Preparation of N¹ -(4-chlorophenyl)-N⁵-(3,4-methylenedioxyphenyl)-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³-(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amountof N¹ -cyano-N³ -(3,4-methylenedioxyphenyl)-guanidine, 19.7 g of thecaptioned compound was obtained.

White edged crystals mp. 237°˜239° C.

Elemental analysis C₁₅ H₁₅ Cl₂ N₅ O₂

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   48.93         4.11   8.69                                            Found    48.76         3.95   8.47                                            ______________________________________                                    

EXAMPLE 34 Preparation of N¹ -(4-chlorophenyl)-N⁵-(3,4-methylenedioxibenzyl)-biguanide hydrochloride

In the same manner as in Example 2 except that N¹ -cyano-N³ -(3,4-dichlorobenzyl)-guanidine was replaced by the equimolecular amount of N¹-cyano-N³ -(3,4-methylenedioxybenzyl)-guanidine, 22.4 g of the captionedcompound was obtained.

White edged crystals mp. 231°˜233° C.

Elemental analysis C₁₆ H₁₇ Cl₂ N₅ O₂

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   50.27         4.48   18.32                                           Found    50.44         4.29   18.31                                           ______________________________________                                    

EXAMPLE 35 Preparation of N¹ -(4-chlorobenzyl)-N⁵ -octyl-biguanidehydrochloride

In the same manner as in Example 1 except that 3,4-dichlorobenzylaminehydrochloride was replaced by the equimolecular amount of2,4-chlorobenzylamine hydrochloride, 21.3 g of the captioned compoundwas obtained.

White edged crystals mp. 156°˜158° C.

Elemental analysis C₁₇ H₂₉ Cl₂ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   54.54         7.81   18.71                                           Found    54.76         7.68   18.69                                           ______________________________________                                    

EXAMPLE 36 Preparation of N¹ -(4-chlorobenzyl)-N⁵-(4-chlorobenzyl)-biguanide hydrochloride

Using 20.85 g of N¹ -cyano-N⁵ -(4-chlorobenzyl)-guanidine and 17.8 g of4-chlorobenzylamine hydrochloride, 21.4 g of the captioned compound wasobtained by operating the same manner as in Example 1.

White edged crystals mp. 200°˜202° C.

Elemental analysis C₁₆ H₁₈ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   49.69         4.69   18.11                                           Found    49.62         4.61   18.37                                           ______________________________________                                    

EXAMPLE 37 Preparation of N¹ -(4-chlorobenzyl)-N⁵ -decyl-biguanidehydrochloride

In the same manner as in Example 36 except that 4-chlorobenzylaminehydrochloride was replaced by the equimolecular amount of decylaminehydrochloride, 24.3 g of the captioned compound was obtained.

White edged crystals mp. 161°˜163° C.

Elemental analysis C₁₉ H₃₃ Cl₂ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   56.71         8.27   17.40                                           Found    56.60         8.12   17.63                                           ______________________________________                                    

EXAMPLE 38 Preparation of N¹ -(4-chlorobenzyl)-N⁵ -dodecyl-biguanidehydrochloride

In the same manner as in Example 36 except that 4-chlorobenzylaminehydrochloride was replaced by the equimolecular amount of dodecylaminehydrochloride, 22.3 g of the captioned compound was obtained.

White edged crystals mp. 158°˜160° C.

Elemental analysis C₂₁ H₃₇ Cl₂ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   58.59         8.66   16.27                                           Found    58.41         8.53   16.55                                           ______________________________________                                    

EXAMPLE 39 Preparation of N¹ -(4-chlorobenzyl)-N⁵ -isobutyl-biguanidehydrochloride

In the same manner as in Example 36 except that 4-chlorobenzylaminehydrochloride was replaced by the equimolecular amount of isobutylaminehydrochloride, 18.7 g of the captioned compound was obtained.

White edged crystals mp. 210°˜221° C.

Elemental analysis C₁₃ H₂₁ Cl₂ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   49.06         6.65   22.01                                           Found    48.87         6.52   22.23                                           ______________________________________                                    

EXAMPLE 40 Preparation of N¹ -(4-chlorobenzyl)-N⁵-(3,4-dichlorophenyl)-biguanide hydrochloride

In the same manner as in Example 36 except that 4-chlorobenzylaminehydrochloride was replaced by the equimolecular amount of3,4-dichloraniline hydrochloride, 21.7 g of the captioned compound wasobtained.

White edged crystals mp. 183°˜185° C.

Elemental analysis C₁₅ H₁₅ Cl₄ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   44.25         3.71   17.20                                           Found    44.37         3.66   17.42                                           ______________________________________                                    

EXAMPLE 41 Preparation of N¹ -(3,4-dichlorophenyl)-N⁵-(3,4-methylenedioxybenzyl)-biguanide hydrochloride

Using 21.5 g of N¹ -cyano-N³ -(3,4-dichlorophenyl)-guanidine and 18.8 gof 3,4-methylenedioxybenzylamine hydrochloride, 27.3 g of the captionedcompound was obtained by operating the same manner as in Example 1.

White edged crystals mp. 175°˜177° C.

Elemental analysis C₁₆ H₁₆ Cl₃ N₅ O₂

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   46.12         3.87   16.81                                           Found    46.01         3.76   16.97                                           ______________________________________                                    

EXAMPLE 42 Preparation of N¹ -(3,4-dichlorophenyl)-N⁵ -hexyl-biguanidehydrochloride

In the same manner as in Example 41 except that3,4-methylenedioxybenzylamine hydrochloride was replaced by theequimolecular amount of hexylamine hydrochloride, 22.3 g of thecaptioned compound was obtained.

White edged crystals mp. 154°-156° C.

Elemental analysis C₁₄ H₂₂ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   45.85         6.05   19.10                                           Found    45.66         6.17   19.03                                           ______________________________________                                    

EXAMPLE 43 Preparation of N¹ -(3,4-dichlorophenyl)-N⁵ -decyl-biguanidehydrochloride

In the same manner as in Example 41 except that3,4-methylenedioxybenzylamine hydrochloride was replaced by theequimolecular amount of decylamine hydrochloride, 24.2 g of thecaptioned compound was obtained.

White edged crystals mp. 131°˜133° C.

Elemental analysis C₁₈ H₃₀ Cl₃ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   51.13         7.15    6.56                                           Found    51.02         7.32   16.37                                           ______________________________________                                    

EXAMPLE 44 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidelactate

Dissolving 20 g of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidehydrochloride in 200 ml of methanol, 24.5 ml of 5N NaOH was added, andthe solvent was distilled away. The residual white solid was washed withwater, suspended in 200 ml of water off, and 13 g of lactic acid wasadded, and dissolved by heating. Chilled in ice, precipitating crystalswere filtered, and 12.14 g of the captioned compound was obtained.

White edged crystals mp. 45°˜46° C.

EXAMPLE 45 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanideglycolate

The captioned compound was obtained in the same manner as in Example 44except that lactic acid was replaced by glycolic acid.

White edged crystals mp. 109°˜110° C.

EXAMPLE 46 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidemonomethanesulfonate

The captioned compound was obtained in the smae manner as in Example 44except that lactic acid was replaced by methanesulfonic acid.

White edged crystals mp. 174°˜176° C.

EXAMPLE 47 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidehydrobromade

The captioned compound was obtained in the same manner as in Example 44except that lactic acid was replaced by 47% hydrobromic acid.

White edged crystals mp. 120°˜121° C.

EXAMPLE 48 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidephosphate

The captioned compound was obtained in the same manner as in Example 44except that lactic acid was replaced by phosphoric acid.

White edged crystals mp. 96°˜98° C.

EXAMPLE 49 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidedimethanesulfonate

Dissolving 25 g of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidehydrochloride in 250 ml of methanol, 30.6 ml of 5N NaOH was added, andthe solvent was distilled away. The residual white solid was washed withwater, and dissolved in 500 ml of acetone, and 14.7 g of methanesulfonicacid was added. The precipitating crystals were filtered off, and byrecrystallizing from ethanol-ether, 25.8 g of the captioned compound wasobtained.

White edged crystals mp. 171°˜172° C.

Elemental analysis C₁₇ H₂₇ N₅ Cl₂.2CH₃ SO₃ H

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   40.42         6.25   12.41                                           Found    40.40         6.55   12.31                                           ______________________________________                                    

REFERENCE EXAMPLE Preparation of N¹ -(3,4-dichlorobenzyl)-N³-cyanoguanidine

Putting 63.7 g (300 mM) of 3,4-dichlorobenzylamine hydrochloride and30.9 g (1.1 eq.) of sodium dicyanamide in 950 ml (15 V) of acetonitrile,the mixture was heated and refluxed for 3.5 hours. Distilling away thesolvent, 600 ml of water was added to the residue (white solid) todisperse and wash. Obtained crystals were filtered off, and dispersedand washed in 600 ml of dichloromethane. Since residue of amine wasrecognized, the crystals were dispersed and washed again in 600 ml ofwater and 500 ml of dichloromethane. Crystals were filtered off, anddried overnight at 60° C., and 57.7 g (78.9%) of the captioned compoundwas obtained.

White crystals mp. 173° C.

Elemental analysis C₉ H₈ Cl₂ N₄

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   44.47         3.32   23.05                                           Found    44.32         3.08   23.30                                           ______________________________________                                    

EXAMPLE 50 Preparation of N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidedihydrochloride

Suspending 10.0 g (41.1 mM) of N¹ -(3,4-dichlorobenzyl)-N³-cyanoguanidine and 5.31 g (1.0 eq.) of n-octylamine in 100 ml ofxylene, 3.5 ml (1.1 eq.) of concentrated hydrochloric acid was added andstirred for several minutes. The reaction was continued for 8 hours inreflux by using Dean-Stark trap. Distilling away the solvent, and byethanol coboiling, xylene was removed. The residue was dissolved in 40ml of 70% acetonitrile, and 6.8 ml (2.0 eq.) of concentratedhydrochloric acid was added. Further adding 90 ml of 70% acetonitrile,the mixture was recrystallized. Obtained cystals were filtered off,dried overnight at 60° C., and 14.3 g (78.2%) of white crystallineproduct was obtained. The obtained rough crystals were recrytallizedtwice with 70% acetonitrile (6 to 7 V), and 7.16 g (50.1%) of thecaptioned compound was obtained.

mp. 176°˜178° C.

Elemental analysis C₁₇ H₂₉ Cl₄ N₅

    ______________________________________                                               C           H      N                                                   ______________________________________                                        Calcd.   45.86         6.56   15.73                                           Found    45.54         6.66   15.79                                           ______________________________________                                    

Meanwhile, when the produced material (dihydrochloride) wasrecrystallized in a solvent of high water content (such as CH₃ CN,ethanol), it was converted into the same monohydrochloride as obtainedin Example 1.

    ______________________________________                                        Prescription 1 of disinfectant                                                Monobiguanide derivative of Example 1                                                                   5      g                                            Nonionic surface active agent                                                                           3.75   g                                            (Polyoxyethylene phenylether)                                                 Distilled water for injection                                                                           proper                                              Whole volume              100    ml                                           Prescription 2 of disinfectant                                                Monobiguanide derivative of Example 1                                                                   0.5    g                                            Nonionic surface active agent                                                                           0.375  g                                            (Polyoxyethylene phenylether)                                                 Ethanol                   83     ml                                           Distilled water for injection                                                                           proper                                              Whole volume              100    ml                                           ______________________________________                                    

Antibacterial activity test

In order to test the antibacterial action of the compounds obtained inthe examples in various organisms, the minimum inhibitory concentration(MIC) was determined according to the standard method of Japan Societyof Chemotherapy. The culture medium for sensitivity disc was used(Chemotherapy, vol. 29, No. 1, 76-79, 1981). As the control drug,gluconic chlorohexydine (tradename "Hibiten" commercially available fromSumitomo Pharmaceutical) was used and tested similarly. The results areshown in Table 1.

The inoculum size was adjusted to 1×10⁶ cells/ml (0.07 to 0.16 at O.D.600 nm).

                                      TABLE 1                                     __________________________________________________________________________                 MIC μg/ml (10.sup.6 cells/ml)                                 __________________________________________________________________________                 Examples                                                         Strain       1   2   3   4   5   6   7   8   9   10                           __________________________________________________________________________    S. aureus FDA 209P                                                                         1.56                                                                              1.56                                                                              3.13                                                                              1.56                                                                              0.78                                                                              3.13                                                                              1.56                                                                              1.56 1.56                                                                              0.78                        S. aureus MRSA 57                                                                          1.56                                                                              3.13                                                                              3.13                                                                              1.56                                                                              1.56                                                                              3.13                                                                              1.56                                                                              1.56 1.56                                                                              0.39                        E. coli NIHJ JC-2                                                                          100 12.5                                                                              6.25                                                                              100 50  12.5                                                                              6.25                                                                              12.5 25  6.25                        K. pneumoniae NCTC 9632                                                                    --  --  --  --  --  --  --  --   --  --                          S. marcescens IFO 12648                                                                    100 25  100 100 50  25  25  25   25  6.25                        P. aeruginosa ATCC 10145                                                                   100 25  100 100     100 50  100  100 25                          A. calcoaceticus Ac-54                                                                     25  12.5                                                                              12.5                                                                              100 25  12.5                                                                              6.25                                                                              12.5 6.25                                                                              3.13                        __________________________________________________________________________                 Examples                                                         Strain       11  12   13 14  15  16  17  18   19  20                          __________________________________________________________________________    S. aureus FDA 209P                                                                         1.56                                                                              1.56                                                                              12.5                                                                              1.56                                                                              3.13                                                                              1.56                                                                              1.56                                                                              0.78 6.25                                                                              6.25                        S. aureus MRSA 57                                                                          0.78                                                                              1.56                                                                              12.5                                                                              1.56                                                                              3.13                                                                              1.56                                                                              1.56                                                                              0.78 6.25                                                                              6.25                        E. coli NIHJ JC-2                                                                          6.25                                                                              12.5                                                                              50  100 25  100 100 12.5 25  25                          K. pneumoniae NCTC 9632                                                                    --  --  --  --  --  --  --  --   --  --                          S. marcescens IFO 12648                                                                    12.5                                                                              25  50  50  100 100 100 12.5 50  50                          P. aeruginosa ATCC 10145                                                                   50  50  100 100 100 100 100 100  100 100                         A. calcoaceticus Ac-54                                                                     6.25                                                                              12.5                                                                              100 6.25                                                                              12.5                                                                              100 12.5                                                                              6.25 50  50                          __________________________________________________________________________                 Examples                                                         Strain       21  22  23  24  25  26  27  28   29  30                          __________________________________________________________________________    S. aureus  FDA 209P                                                                        12.5                                                                              1.56                                                                              3.13                                                                              6.25                                                                              1.56                                                                              6.25                                                                              6.25                                                                              6.25 6.25                                                                              3.13                        S. aureus MRSA 57                                                                          12.5                                                                              1.56                                                                              3.13                                                                              6.25                                                                              1.56                                                                              6.25                                                                              6.25                                                                              6.25 6.25                                                                              0.78                        E. coli NIHJ JC-2                                                                          100 100 50  100 25  50  25  25   12.5                                                                              12.5                        K. pneumoniae NCTC 9632                                                                    --  --  --  --  --  25  --  --   --  --                          S. marcescens IFO 12648                                                                    100 100 50  100 25  100 50  50   25  12.5                        P. aeruginosa ATCC 10145                                                                   100 100 100 100 100 100 100 100  100 25                          A. calcoaceticus Ac-54                                                                     100 100 50  100 25  100 12.5                                                                              12.5 12.5                                                                              6.25                        __________________________________________________________________________                 Examples                                                         Strain       31  32  33  34  35  36  37  38   39  40                          __________________________________________________________________________    S. aureus FDA 209P                                                                         1.56                                                                              25  50  25  3.13                                                                              3.13                                                                              1.56                                                                              6.25 12.5                                                                              1.56                         S. aureus MRSA 57                                                                         0.78                                                                              12.5                                                                              50  25  3.13                                                                              3.13                                                                              1.56                                                                              6.25 12.5                                                                              1.56                        E. coli NIHJ JC-2                                                                          12.5                                                                              100 100 100 100 25  100 100  50  12.5                        K. pneumoniae NCTC 9632                                                                    --              --  --  --  --   50  --                          S. marcescens IFO 12648                                                                    12.5                                                                              100 100 100 100 25  100 100  100 12.5                        P. aeruginosa ATCC 10145                                                                   25  100 100 100 100 100 100 100  100 100                         A. calcoaceticus Ac-54                                                                     6.25                                                                              100 100 100 25  25  100 100  50  6.25                        __________________________________________________________________________                 Examples                                                                                                        Control                        Strain        41  42   43  44    45  46    49  agent                          __________________________________________________________________________    S. aureus FDA 209P                                                                          12.5                                                                              3.13 6.25                                                                              1.56  1.56                                                                              1.56  1.56                                                                              1.56                           S. aureus MRSA 57                                                                           6.25                                                                              3.13 6.25                                                                              1.56  1.56                                                                              3.13  3.13                                                                              1.56                           E. coli NIHJ JC-2                                                                           25  12.5 100 100   100 100   100 1.56                           K. pneumoniae NCTC 9632                                                                     --  --   50  --    --  --    --  --                             S. marcescens IFO 12648                                                                     25  6.25 100 100   100 100   100 25                             P. aeruginosa ATCC 10145                                                                    100 6.25 100 100   100 100   100 100                            A. calcoaceticus Ac-54                                                                      25  12.5 100 25    25  25    50  12.5                           __________________________________________________________________________

Bactericidal activity test

As to the compounds obtained in Examples 1 and 2, the bactericidalactivity at room temperature (25° C.) was measured by treating in ashort time by reference to the phenol coefficient measurement method.

(1) Culture medium

For prior culture of test organism, Mueller Hinton Broth (DIFCD) wasused. As growth culture medium of surviving cells in the test solutionafter bactericidal treatment, SCDLP culture medium inactivated bydisinfectant was used ("Daigo" commercially available from NipponSeiyaku).

(2) Test method

The compound obtained in each examples was dissolved in distilled water,and adjusted to a double concentration of the test concentration, andafter aseptic filtering, the solution was diluted in steps of 1/2 in arange of Specified test concentration, and 50 μl was dispensed in96-well microplate. On the other hand, the test organism undergoing theprior culture for 16 hours twice was adjusted to 10⁸ cells/ml withsterilized distilled water in order to eliminate the effects of culturemedium (0.3 at O.D. 660 nm), and diluted to 1/100 with 5 ml or 10 ml ofsterilized distilled water to obtain 10⁶ cells/ml, and into 50 μl of thetest solution in the microplate, an equivalent 50 μl was injected andmixed. After the lapse of 1 minute and 3 minutes, 5 μl of the testsolution was taken out from the microplate, and was suspended in 150 μlof inactivated culture medium, and was cultivated for 16 to 18 hours at37° C. The survival of organisms in the test solution was judged by theturbidity, and the minimum bactericidal concentration in lapse of 1minute and 3 minutes was determined. The result is shown in Table 2.

                                      TABLE 2                                     __________________________________________________________________________                 Minimum Bactericidal Concentration μg/ml (10.sup.6                         cells/ml)                                                                     Example 1                                                                             Example 2                                                                             Control agent                                    Strain       1 min.                                                                            3 min.                                                                            1 min.                                                                            3 min.                                                                            1 min. 3 min.                                    __________________________________________________________________________    S. aureus FDA 209P                                                                         12.5                                                                              3.13                                                                              500 100 >1000  25                                        S. aureus MRSA 57                                                                          6.25                                                                              ≦1.56                                                                      200 25  >1000  50                                        E. coli NIHJ JC-2                                                                          3.13                                                                              ≦1.56                                                                      25  6.25                                                                              12.5   6.25                                      K. pneumoniae NCTC 9632                                                                    3.13                                                                              3.13                                                                              12.5                                                                              12.5                                                                              3.13   ≦1.56                              S. marcescens IFO 12648                                                                    6.25                                                                              ≦1.56                                                                      25  6.25                                                                              12.5   6.25                                      A. calcoaceticus Ac-54                                                                     3.13                                                                              3.13                                                                              12.5                                                                              6.25                                                                              6.25   6.25                                      P. aeruginosa ATCC 10145                                                                   3.13                                                                              3.13                                                                              12.5                                                                              6.25                                                                              12.5   6.25                                      P. cepacia 2315-C0010                                                                      200 50  200 50  >1000  >1000                                     __________________________________________________________________________

Thus, the monobiguanide derivative (1) of the invention or its saltpossesses a high bactericidal action and antibacterial action, and henceit may be preferably used as the disinfectant for the human or animalskin or the like.

Next, the examples of bis-biguanide derivative (2) of this invention areexplained.

EXAMPLE 51 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-bis[5-(4-chlorophenyl)biguanide]dihydrochloride

Refluxing 33 g (0.15 mols) of 1,3-di(aminomethyl) cyclohexanedihydrochloride and 26 g (0.3 mols) of dicyanamide sodium in buthanolfor 12 hours at temperature of 140° C., 51.3 g of1,1'-[1,3-cyclohexanebis(methylene)]-bis(3-cyanoguanidine) was obtained.

Adding 5.52 g (0.02 mols) of this reaction product and 6.56 g (0.04mols) of p-chloroaniline hydrochloride into β-oxyethylether (tradename:Cellosolve), by refluxing for 3 hours at 140° C. to react, 4.3 g ofproduct was obtained. This product was recrystallized and refined inwater and ethanol mixed solvent, and the captioned compound wasobtained.

White edged crystals mp. 245°˜248° C. NMR (CDCl₃ +DMSO-d6) δ: 1.1˜1.9(m, 8H), 2.8˜3.5 (m, 6H), 6.95 (bs), 7.37 (dd, 4H, J=9 Hz 7.90 (bs)

EXAMPLE 52 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-bis[5-(4-iodophenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of p-iodoaniline hydrochloride (Yield 5.1 g).

White edged crystals mp. 259°˜261° C.

EXAMPLE 53 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-bis[5-(4-bromophenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of p-bromoaniline hydrochloride (Yield 4.7 g).

White edged crystals mp. 265°˜267° C.

EXAMPLE 54 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(2,4-dichlorophenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of 2,4-dichloroaniline hydrochloride (Yield 5.7 g).

White edged crystals mp. 261°˜265° C.

EXAMPLE 55 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(2,4-difluorophenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of 2,4-difluoroaniline hydrochloride (Yield 4.1 g).

White edged crystals mp. 212°˜215° C.

EXAMPLE 56 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(4-t-butylphenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of p-t-butylaniline hydrochloride (Yield 3.6 g).

White edged crystals mp. 194°˜197° C.

EXAMPLE 57 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(3,4-dimethylphenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of 3,4-dimethylaniline hydrochloride (Yield 3.8 g).

Pale yellow edged crystals mp. 162°˜166° C.

EXAMPLE 58 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(4-ethylthiophenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of p-ethylthioaniline hydrochloride (Yield 5.4 g).

mp. 110°˜113° C.

EXAMPLE 59 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(3-trifluoromethylphenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of p-trifluoromethylaniline hydrochloride (Yield2.5 g).

White edged crystals mp. 240°˜242° C.

EXAMPLE 60 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(2-ethylhexyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of p-(2-ethylhexyl)aniline hydrochloride (Yield 4.6g).

White edged crystals mp. 105°˜107° C.

EXAMPLE 61 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(3,4-dichlorobenzyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of 3,4-dichlorobenzylamine hydrochloride (Yield 5.3g).

White edged crystals mp. 231°˜233° C.

EXAMPLE 62 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-(3,4-dichlorophenyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of 3,4-dichloraniline hydrochloride (Yield 3.7 g).

White edged crystals mp. 259°˜261° C.

EXAMPLE 63 Preparation of1,1'-[1,3-cyclohexanebis(methylene)]-[5-benzylbiguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of benzylamine hydrochloride (yield 5.9 g).

White edged crystals mp. 208°˜211° C.

EXAMPLE 64 Preparation of1,1-'[1,3-cyclohexanebis(methylene)]-[5-(4-chlorobenzyl)biguanide]dihydrochloride

The captioned compound was obtained in the same manner as in Example 51except that p-chloroaniline hydrochloride was replaced by theequimolecular amount of 4-chlorobenzylamine hydrochloride (Yield 4.4 g).

White edged crystals mp. 204°˜207° C.

    ______________________________________                                        Prescription 3 of disinfectant                                                Gluconic acid salt of Example 51                                                                       5      g                                             Nonionic surface active agent                                                                          3.75   g                                             (Polyoxyethylene phenylether)                                                 Distilled water for injection                                                                          proper                                               Whole volume             100    ml                                            Prescription 4 of disinfectant                                                Gluconic acid salt of Example 51                                                                       0.5    g                                             Nonionic surface active agent                                                                          0.375  g                                             (Polyoxyethylene phenylether)                                                 Ethanol                  8.3    ml                                            Distilled water for injection                                                                          proper                                               Whole volume             100    ml                                            ______________________________________                                    

Antibacterial activity test

To investigate the antibacterial actions of the compounds obtained inExamples 51 to 64, the minimum inhibitory concentration (MIC) wasdetermined by employing the standard method of Japan Society ofChemotherapysame as mentioned above. The results are shown in Table 3.

                                      TABLE 3                                     __________________________________________________________________________                 MIC μg/ml (10.sup.6 cells/ml)                                 __________________________________________________________________________                 Examples                                                         Strain       51  52   53  54   55  56    57                                   __________________________________________________________________________    S. aureus FDA 209P                                                                         0.39                                                                              0.39 0.39                                                                              0.78 3.13                                                                              3.13  1.56                                 S. epidermidis ATCC 12228                                                                  0.39                                                                              0.39 0.39                                                                              0.39 3.13                                                                              1.56  1.56                                 E. coli NIHJ JC-2                                                                          3.13                                                                              6.25 3.13                                                                              6.25 25  25    12.5                                 S. typhi NCTC 8393                                                                         1.56                                                                              6.25 3.13                                                                              6.25 6.25                                                                              12.5  6.25                                 S. marcescens IFO 12648                                                                    6.25                                                                              12.5 6.25                                                                              50   50  50    50                                   P. aeruginosa ATCC 10145                                                                   12.5                                                                              100  25  50   100 >100  100                                  C. alficans IFO 1385                                                                       3.13                                                                              6.25 6.25                                                                              6.25 25  50    100                                  A. fumigatus IFM 4942                                                                      125 250  125 250  400 >400  >400                                 __________________________________________________________________________                 Examples                                                                                                  Control                              Strain       59    61    62  63    64    agent                                __________________________________________________________________________    S. aureus FDA 209P                                                                         1.56  3.13  0.78                                                                              3.13  1.56  1.56                                 S. epidermidis ATCC 12228                                                                  1.56  1.56  0.39                                                                              1.56  1.56  0.78                                 E. coli NIHJ JC-2                                                                          12.5  12.5  6.25                                                                              25    25    1.56                                 S. typhi NCTC 8393                                                                         6.25  12.5  6.25                                                                              25    6.25  1.56                                 S. marcescens IFO 12648                                                                    25    50    25  50    25    25                                   P. aeruginosa ATCC 10145                                                                   >100  >100  100 >100  >100  >100                                 C. alficans IFO 1385                                                                       100   100   6.25                                                                              100   100   5                                    A. fumigatus IFM 4942                                                                      >200  >200  125 >200  >200  >200                                 __________________________________________________________________________

What is claimed is:
 1. A biguanide derivative or its salt selectedfrom:N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide or its salt, N¹-(3,4-dichlorophenyl)-N⁵ -octyl-biguanide or its salt, N¹-(3,4-dichlorobenzyl)-N⁵ -(n-decyl)-biguanide or its salt, N¹-(3,4-dichlorobenzyl)-N⁵ -(1,1,3,3-tetramethylbutyl)-biguanide or itssalt, N¹ -(3,4-dichlorobenzyl)-N⁵ -hexyl-biguanide or its salt, N¹-(3,4-dichlorobenzyl)-N⁵ -(2-ethoxyethyl-(biguanide or its salt, N¹-(3,4-dichlorobenzyl)-N⁵ -[2-(2-hydroxyethoxy)ethyl]-biguanide or itssalt, N¹ -(3,4-dichlorobenzyl)-N⁵ -(3-diethylaminopropyl)-biguanide orits salt, N¹ -(3,4-dichlorobenzyl)-N⁵-[(2-diethylamino)-ethyl]-biguanide or its salt, N¹-(3,4-dichlorobenzyl)-N⁵ -[3-(di-n-butylamino)propyl]-biguanide or itssalt, N¹ -(3,4-dichlorophenyl)-N⁵ -hexyl-biguanide or its salt, and N¹-(3,4-dichlorophenyl)-N⁵ -decyl-biguanide or its salt.
 2. A biguanidederivative or its salt selected from:N¹ -(3,4-dichlorobenzyl)-N⁵-octyl-biguanide or its salt, and N¹ -(3,4-dichlorophenyl)-N⁵-octyl-biguanide or its salt.
 3. N¹ -(3,4-Dichlorobenzyl)-N⁵-octyl-biguanide or its salt.
 4. The biguanide or its salt of claim 3,selected from:N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanidehydrochloride, N¹ -(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide lactate, N¹-(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide glucolate, N¹-(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide monomethaesulfonate, N¹-(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide hydrobromide, N¹-(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide phosphate, N¹-(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide dimethanesulfonate, and N¹-(3,4-dichlorobenzyl)-N⁵ -octyl-biguanide dihydrochloride.
 5. Adisinfectant composition comprising an effective amount of the biguanidederivative or its salt of claim 1, and its carrier.
 6. A disinfectantcomposition comprising an effective amount of the biguanide derivativeor its salt of claim 2, and its carrier.
 7. A disinfectant compositioncomprising an effective amount of the biguanide or its salt of claim 3,and its carrier.